Unveiling the role of hydroxyapatite and hydroxyapatite/silver composite in osteoblast-like cell mineralization: An exploration through their viscoelastic properties.

Mechanical properties are becoming fundamental for advancing the comprehension of cellular processes. This study addresses the relationship between viscoelastic properties and the cellular mineralization process. Osteoblast-like cells treated with an osteogenic medium were employed for this purpose. Additionally, the study explores the impact of hydroxyapatite (HA) and hydroxyapatite/silver (HA/Ag) composite on this process. AFM relaxation experiments were conducted to extract viscoelastic parameters using the Fractional Zener (FZ) and Fractional Kelvin (FK) models. Our findings revealed that the main phases of mineralization are associated with alterations in the viscoelastic properties of osteoblast-like cells. Furthermore, HA and HA/Ag treatments significantly influenced changes in the viscoelastic properties of these cells. In particular, the HA/Ag treatment demonstrated a marked enhancement in cell fluidity, suggesting a possible role of silver in accelerating the mineralization process. Moreover, the study underscores the independence observed between fluidity and stiffness, indicating that modifications in one parameter may not necessarily correspond to changes in the other. These findings shed light on the factors involved in the cellular mineralization process and emphasize the importance of using viscoelastic properties to discern the impact of treatments on cells.

Methodologies and models for measuring viscoelastic properties of cancer cells: Towards a universal classification.

Different methods and several physical models exist to study cell viscoelasticity with the atomic force microscope (AFM). In search of a robust mechanical classification of cells through AFM, in this work, viscoelastic parameters of the cancer cell lines MDA-MB-231, DU-145, and MG-63 are obtained using two methodologies; through force-distance and force-relaxation curves. Four mechanical models were applied to fit the curves. The results show that both methodologies agree qualitatively on the parameters that quantify elasticity but disagree on the parameters that account for energy dissipation. The Fractional Zener (FZ) model represents well the information given by the Solid Linear Standard and Generalized Maxwell models. The Fractional Kelvin (FK) model concentrates the viscoelastic information mainly in two parameters, which could be an advantage over the other models. Therefore, the FZ and FK models are proposed as the basis for the classification of cancer cells. However, more research using these models is needed to obtain a broader view of the meaning of each parameter and to be able to establish a relationship between the parameters and the cellular components.

Ultrastructural changes associated to the neuroendocrine transdifferentiation of the lung adenocarcinoma cell line A549.

The neuroendocrine transdifferentiation has been found in many cancer cell types, such as prostate, lung and gastrointestinal cells and is accompanied by a lower patient life expectancy. The transdifferentiation process has been induced in vitro by the exposure to different stimuli in human lung adenocarcinoma. The aim of this work was to identify the morphological characteristics of the neuroendocrine phenotype in a human lung cancer cell line, induced by two cAMP elevating agents (IBMX and FSK). Our results showed two phenotypes, one produced by IBMX with higher volume, cell size and increased number of secondary projections, and the other produced by FSK with higher area, roughness of the membrane, cell neurite percentage, number of outgrowths per cell and increased number of primary projections. In conclusion, we describe some morphological and ultrastructural characteristics of the neuroendocrine phenotype in A549 human lung cancer cell line promoted by IBMX and FSK to contribute to the understanding of the autocrine or paracrine signaling within the tumor microenvironment.

Viscoelastic properties of doxorubicin-treated HT-29 cancer cells by atomic force microscopy: the fractional Zener model as an optimal viscoelastic model for cells.

The malignancy of cancer cells and their response to drug treatments have been traditionally studied using solely their elastic properties. However, the study of the combined viscous and elastic properties provides a richer description of the mechanics of the cell, and achieves a more precise assessment of the effect exerted by anti-cancer treatments. We used an atomic force microscope to obtain the morphological, elastic and viscous properties of HT-29 colorectal cancer cells. Changes in these parameters were observed during exposure of the cells to doxorubicin at different times. The elastic properties were analyzed using the Hertz and Sneddon models. Furthermore, we analyzed the data to study the viscoelasticity of the cells comparing the models known as the standard linear solid, fractional Zener, generalized Maxwell, and power law. A discussion about the optimal model based in the accuracy and physical assumptions for this particular system is included. From the morphological data and viscoelasticity of HT-29 cells exposed to doxorubicin, we found that some parameters were affected differently at shorter or longer exposure times. For instance, the relaxation time suggests a measure of the cell to self-heal and it was observed to increase at shorter exposure times and then to reduce for longer exposure times to the drug. The fractional Zener model better described the mechanical properties of the cell due to the reduced number of parameters and the quality of the fit to experimental data.